Category Archives: Hormone Therapy

Yana Vinogradova, PhDResearch Fellow
Department of Primary Care
School of Medicine
University of Nottingham
University Park, Nottingham

MedicalResearch.com: What is the background for this study?

Response: The study targeted middle age women going through menopause. This is the stage of life when women naturally reach the end of their reproductive life and their hormones gradually decrease. Some women experience unpleasant effects such as hot flushes, night sweats, mood swings, memory and concentration loss, headaches. Quality of life may be severely affected. Hormone replacement therapy uses a class of drugs, which, like all drugs, have side effects. VTE is a serious side effect which can have a lethal outcome.

There are different preparations of hormones available for such women. Some of them were extensively studied in a large American Trial Women’s Health Initiative and showed the risk of VTE to be twice as high for women who took them. However, these well-studied drugs are mostly prescribed in America. The more popular drugs in Europe and the UK have been much less studied, so it was unclear how they compared.Continue reading →

Jerilynn C. Prior, MD
Professor in the Department of Medicine
Division of Endocrinology and Metabolism
University of British Columbia in Vancouver

Dr. Prior has written the second edition of the award-winning book, Estrogen’s Storm Season—Stories of Perimenopause this year as an ebook on Google Play.

MedicalResearch.com: What is the background for this study?

Response: There is an urgent need for an effective therapy for perimenopausal hot flushes/flashes and night sweats (vasomotor symptoms, VMS). Although often considered “estrogen deficiency symptoms” VMS are common and very problematic for women in the menopause transition and who have not yet been one year without flow. About 23% of North American women are now in the perimenopausal age range. Surprisingly VMS are more common in perimenopause than in menopause; 9% of perimenopausal women have severe VMS as classified by the FDA, meaning more than 50 VMS per week of moderate to intense severity.

The commonly used therapies for VMS in midlife women have not been proven more effective than placebo! That includes combined hormonal contraceptives (CHC) and menopausal-type hormone therapy (MHT) as well as the SSRI/SNRI anti-depressants and gabapentin.Continue reading →

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: ​Previous research has shown that estradiol treatment after menopause can reduce the stress response when exposed to a stressor, including the cortisol response to stress. Other work has shown that stress can impair certain types of memory​. We wanted to test whether post-menopause estradiol treatment would not only attenuate the cortisol response to stress, but if it could also reduce the negative effects of stress on memory. In particular, we tested the effects on a type of memory called working memory. Working memory allows us to maintain and update information we need to readily access in short-term memory. For example, imagine you stop at the grocery store after work and only have a mental list of the items you need to make dinner. Working memory is the memory type engaged in helping you maintain and update your mental list of items as you grab items off the shelves and check them off your list.

We recruited women through the Early versus Late Intervention Trial with Estradiol, a randomized, double-blinded, placebo-controlled clinical trial. Women who participated in our study had received nearly 5 years of either estradiol or placebo.

We found that women receiving estradiol showed significantly smaller cortisol responses to stress and less of an effect of stress on working memory than women that had been receiving placebo.

Response: The current report provides new information on total mortality and the rates of death from specific causes (cardiovascular disease, cancer, other major illnesses) over 18 years of follow-up in the Women’s Health Initiative (WHI) randomized trials of hormone therapy (estrogen + progestin and estrogen alone). This is the first WHI report to focus on all-cause and cause-specific mortality. It includes all of the 27,347 women in the 2 hormone therapy trials with >98% follow-up over 18 years, during which time 7,489 deaths occurred. This is more than twice as many deaths as were included in earlier reports. The report also provides detailed information on differences in results by age group (ages 50-59, 60-69, 70-79) at time of study enrollment.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Recent reports estimate that 0.6% of adults in the United States, or approximately 1.4 million persons, identify as transgender. Despite gains in rights and media attention, the reality is that transgender persons experience health disparities, and a dearth of research and evidence-based guidelines remains regarding their specific health needs. The lack of research to characterize cardiovascular disease (CVD) and CVD risk factors in transgender populations receiving cross-sex hormone therapy (CSHT) limits appropriate primary and specialty care. As with hormone therapy in cisgender persons (that is, those whose sex assigned at birth aligns with their gender identity), existing research in transgender populations suggests that CVD risk factors are altered by CSHT.

Response: This study was mainly motivated by the absence of available data on the effect of menopausal hormone therapy (MHT) on bone microarchitecture, as well as contradictory results of previous trials regarding the persistence of a residual effect after MHT withdrawal.

We performed a cross-sectional analysis of 1279 postmenopausal women aged 50-80 years participating in OsteoLaus cohort of Lausanne University Hospital. Participants had bone mineral density (BMD) measurement by dual X-ray absorptiometry (DXA) at lumbar spine, femoral neck and total hip, as well as assessment of trabecular bone score (TBS), a textural index that evaluates pixel grey-level variations in the lumbar spine DXA image, providing an indirect index of trabecular microarchitecture.

Response: Researchers are trying to identify a hormonal male contraceptive that is effective, reversible, safe, acceptable, affordable, and available. Most of the research has been done either by groups of university researchers. However, in the 1990s, WHO undertook two multi-center, multinational studies.

The studies were unable to provide evidence to support the development of a commercially viable, and user-acceptable product.

Response: Androgen deprivation therapy is a primary treatment for prostate cancer and works by lowering testosterone levels. There is a strong body of research suggesting that low testosterone can negatively impact neurovascular health and function. We were therefore interested in whether androgen deprivation therapy is associated with dementia through an adverse impact on underlying neurovascular function.

Response: Abuse of anabolic androgenic steroids has become highly prevalent among young men involved in recreational strength training. A recent meta-analysis estimated that approximately 18% of young men involved recreational strength training abuse anabolic steroids.

Well-known adverse effects following abuse of anabolic steroids include hypogonadism (For those who have interest, we have recently published a paper concerning this issue, it can be read and downloaded at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161208).

Yet, we have a poor understanding on the adverse effects these compounds might have on the metabolism and insulin sensitivity.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: A rapid decline in estrogen with menopause may be associated with an increased risk of Alzheimer’s disease risk in women. This study was conducted in newly postmenopausal women who received 17β-Estradiol via a skin patch or conjugated equine estrogen orally or placebo.

Those who received 17β-Estradiol patch had reduced β-amyloid deposits, the plaques found in the brains of people with Alzheimer’s disease, three years after the end of the hormone therapies.

In the study, women with APOE e4 — one form of the most common gene associated with late-onset Alzheimer’s disease — who received the 17β-Estradiol patch had lower levels of β-amyloid deposits than those who received placebo.

Response: Previous epidemiologic studies have shown that women during their reproductive life are more vulnerable (by a factor of two) to depression than men; this has been particularly evident during peaks of intense fluctuations of ovarian hormones, like the premenstrual, perimenopausal and postpartum periods. Endogenous (natural) female sex hormones, however, have been shown in various experimental studies to possess neuroprotective and anti-depressive properties. Production of these hormones is diminished after menopause; therefore, age at menopause can be used as a proxy of the lifetime exposure to endogenous hormones. Our research hypothesis was whether longer exposure to endogenous sex hormones has a cumulative anti-depressive action, i.e., whether later age at menopause decreases the risk for postmenopausal depression.

Medical Research: What is the background for this study? What are the main findings?

Dr. Martinelli: Hormonal therapies are associated with an increased risk of venous thromboembolism. Patients with acute deep-vein thrombosis or pulmonary embolism require anticoagulation, but women of childbearing potential require also an adequate contraception, as oral anticoagulants cross the placenta potentially leading to embryopathy or fetal bleeding. This study was aimed to evaluate the safety of hormonal therapies together with anticoagulant therapies in terms of recurrent venous thrombosis and uterine bleeding. We demonstrated for the first time that women who take oral anticoagulants can safely use hormonal therapies, as their risk of recurrent venous thromboembolism or uterine bleeding is not increased.

Dr. Arem: In the United States, men are more likely to develop colorectal cancer (CRC) than women. In large prospective studies, researchers observed that women who reported taking menopausal hormone therapy (MHT) containing estrogen had a 30-40% lower risk of colorectal cancer, compared to women who did not report menopausal hormone therapy use, suggesting an anti-carcinogenic role for estrogen.

We investigated the relationship between estrogen exposure (hormonal and reproductive factors) in relation to survival (risk of death) among women diagnosed with colorectal cancer.

MedicalResearch: What are the main findings?

Dr. Arem: We found a 20% lower risk of death overall among women who reported current menopausal hormone therapy use at study entry (HR=0.79, 95% CI 0.66-0.94) and a 24% lower risk of death from colorectal cancer (0.76, 0.59-0.99), compared to women who reported never using menopausal hormone therapy.

Among women in our study, we observed no statistically significant associations for colorectal cancer mortality with oral contraceptive use, menarche age, age at first birth, parity, or menopausal age.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Arem: Our study was designed to investigate a mechanistic role for estrogen on carcinogenesis for research purposes. We do not expect these findings to influence clinical practice or behavior.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Medical Research: What is the background for this study? What are the main findings?

Dr. Zapatero: There is a significant body of evidence from randomized trials showing a significant improvement in clinical outcome with the combination of androgen deprivation and conventional-dose radiotherapy (≤70 Gy) in patients with high-risk and intermediate-risk prostate cancer. However, the optimal duration the optimum duration of androgen deprivation in the setting of high-dose radiotherapy remained to be determined.

The results of our trial (DART01/05) show that 2 years of adjuvant androgen deprivation is superior to 4 months androgen deprivation when combined with plus high-dose radiotherapy in terms of biochemical control, freedom from metastasis and overall survival, particularly in patients with high-risk prostate cancer.

Medical Research: What is the background for this study? What are the main findings?

Response: Androgen deprivation therapy (ADT), commonly achieved with gonadotropin-releasing hormone agonists or antagonists, is a mainstay of prostate cancer therapy. While randomized controlled trials demonstrate that ADT improves survival among men with unfavorable risk prostate cancer, retrospective studies have suggested that some men with comorbid illnesses such as heart disease may not derive a benefit from—or may even be harmed by—ADT. However, the nature of this harm has not been characterized. We studied over 5000 men with prostate cancer who were treated with brachytherapy (implanted radioactive seeds) with or without ADT. We analyzed the men based on pre-treatment cardiac comorbidity and examined the association between ADT and death from cardiac causes. We found that among men with congestive heart failure or a past myocardial infarction (MI), Androgen deprivation therapy was associated with a three-times greater risk of death from heart disease. However, Androgen deprivation therapy was not associated with greater risk of cardiac mortality in men without heart disease or with a risk factor for heart disease, such as diabetes, hypertension or hyperlipidemia.Continue reading →

Professor Arden: We found that in a cohort of women who had used hormone replacement therapy (HRT) and underwent knee or hip replacement their risk of implant revision was reduced by about 40% compared to non-users of HRT.Continue reading →

WHI investigators publish most comprehensive report to date on the two Hormone Therapy Trials and extend follow-up to 13 years: Results inform clinical decision making

Researchers from the Women’s Health Initiative (WHI) Hormone Therapy (HT) Trials provide new information from extended follow-up of postmenopausal women in the two HT trials (estrogen plus progestin and estrogen alone) and the most comprehensive look at the findings to date. The study, published October 2 in the Journal of the American Medical Association, presents information on a wide range of diseases and quality-of-life outcomes, comparisons of the two trials side-by-side, and a full breakdown of results by age and time since menopause onset. The WHI, which enrolled 27,347 women nation-wide in the two hormone therapy trials, is sponsored by the National Institutes of Health.

“Our main goal was to provide as much information as possible from the WHI hormone therapy trials to help women and their clinicians make the most informed decisions about hormone therapy use. The WHI findings, presented in detail by age group and time since menopause onset, help to guide clinical decision making,”, said JoAnn Manson, MD, DrPH, first author of the report and Chief of Preventive Medicine at Brigham and Women’s Hospital. Manson is one of the Principal Investigators of the WHI and the Michael and Lee Bell Professor of Women’s Health at Harvard Medical School .

Key findings of the report are that hormone therapy has a complex pattern of health risks and benefits and that younger women tend to have a more favorable risk-to-benefit profile than older women. The researchers also found that combination estrogen plus progestin (in women with an intact uterus) had more risks than estrogen alone (used in women with hysterectomy), primarily due to an increased risk of breast cancer with the former but not the latter. Both forms of hormone therapy increased the risk of stroke, blood clots in the legs, gallstones, and urinary incontinence, while benefits included decreased risk of hip fractures, other fractures, diabetes, and hot flashes/night sweats. Estrogen plus progestin increased dementia (in women >65 years), but neither treatment affected cognition in younger women. For estrogen alone, younger women (ages 50-59) had more favorable results for all-cause mortality, heart attacks, and colorectal cancer, and their overall risk-to-benefit profile on estrogen alone was more favorable than for older women. Effects on quality-of-life outcomes with HT were mixed, with improvement in sleep and joint pain but increases in breast tendernes.

After stopping hormone therapy, most risks and benefits of hormone therapy dissipated. However, over the 13-yr cumulative follow-up period, breast cancer risk remained slightly elevated for estrogen plus progestin but became significantly reduced for estrogen alone. For estrogen plus progestin, a significant reduction in uterine (endometrial) cancer emerged during follow up and the risk of hip fracture remained significantly (but modestly) reduced. For both forms of hormone therapy, there was no significant increase or decrease in the rate of total cancer (all types combined), cancer mortality, cardiovascular mortality, or all-cause mortality in the overall study population.

The researchers conclude that the findings from the two WHI trials do not support use of hormone therapy for prevention of chronic disease, but treatment is appropriate for symptom management in some women. The absolute risks of adverse events in younger women are lower than in older women, menopausal symptoms are more common in younger age groups, and the quality-of-life benefits are likely to outweigh the risks for many women who seek treatment for symptoms during the menopause transition. “Short-term use of hormone therapy to manage moderate-to-severe hot flashes or other symptoms in early menopause remains appropriate, A clear distinction between the use of hormone therapy for symptom management in women with indications for treatment and its use for the purpose of chronic disease prevention is essential,” added Manson. “Although studies of other hormone therapy formulations , doses, and routes of delivery are needed to find treatments with fewer risks, these medications are now among the best studied treatments in medical history. Clinicians can share information from the WHI trials with their patients and help them make more informed choices.”

Dr. Pahan: While different toxins and a number of complex genetic approaches are used to model Parkinson’s disease in mice, this study delineates that simple castration is sufficient to cause persistent Parkinson’s like pathology and symptoms in male mice. This simple, but persistent, model may be helpful in discovering drugs against Parkinson’s disease. Furthermore, these results suggest that sudden drop of testosterone level could trigger Parkinson’s disease.Continue reading →

Dr. Weickhardt:The study was hoping to confirm our earlier published observation that crizotinib use led to low testosterone in male patients. The earlier study was based on our observation of symptoms of low testosterone in some patients treated with the drug, and had suggested strongly that crizotinib led to rapid decrease in testosterone levels, however this was based only on a single center’s patients, and only 19 patients. We hoped to do this by surveying a larger population of crizotinib treated patients across multiple institutions. We serially measured several relevant hormones.Continue reading →

ROCHESTER, Minn. – Estrogen may prevent strokes in premature or early menopausal women, Mayo Clinic researchers say. Their findings challenge the conventional wisdom that estrogen is a risk factor for stroke at all ages. The study was published in the journal Menopause.

Researchers combined the results from a recent Mayo Clinic study with six other studies from across the world and found that estrogen is protective for stroke before age 50. That is roughly the average age when women go through menopause.

“We were very surprised because these results were unexpected,” says study author Walter Rocca, M.D., an epidemiologist and neurologist at Mayo Clinic. “The old idea that estrogen is always a problem in the brain has to be corrected.” Estrogen can be a problem in older women, he explains, but in younger women, estrogen may be important to protect the brain from strokes.

The study has implications for women who experience premature (before age 40) or early menopause (before age 45) from natural causes or from ovary removal. Women in these groups should consider taking estrogen up to approximately age 50 to prevent stroke, Dr. Rocca says.

Ischemic stroke occurs as a result of an obstruction within a blood vessel supplying blood to the brain. According to the American Stroke Association, these types of strokes account for 87 percent of all stroke cases.

It’s no secret that women often gain weight as they get older. The sex hormone estrogen has an important, if underappreciated, role to play in those burgeoning waistlines.

Now, researchers reporting in the October Cell Metabolism, a Cell Press publication, have traced those hormonal effects on metabolism to different parts of the brain. The findings may lead to the development of highly selective hormone replacement therapies that could be used to combat obesity or infertility in women without the risks for heart disease and breast cancer, the researchers say.

Estrogen acts on receptors found throughout the body, in fat, on ovaries and in muscle. But when it comes to the hormone’s influence on metabolism, Clegg suspected receptors in the brain.

Others had traced the effects of estrogen on energy balance specifically to estrogen receptor-α (ERα). When her team deleted those receptors from the entire brains of mice, “we got very, very fat mice,” Clegg said. The animals consumed more calories and burned less.

The researchers showed female mice lacking ERα in one part of the brain (the hypothalamic steroidogenic factor-1 or SF1 neurons) gained weight without eating any more. Loss of ERα from another brain area (the hypothalamic pro-opiomelanocortin or POMC neurons) had the opposite effect: animals ate more without gaining weight. Loss of ERα receptors in those same neurons also led to various problems in ovulation and fertility.

The findings suggest that drugs developed to specifically target estrogen receptors in the brain might offer a useful alternative to hormone replacement therapies that hit receptors throughout the body. The researchers say they would like to continue to isolate other estrogen-related effects and symptoms, for instance, on hot flashes and cognition.

“The more we know about estrogen’s sites of action, the more likely it is we could develop designer hormone replacement therapies targeting tissue X, Y or Z,” Clegg said.

Fairfax, Va., July 26, 2011 – Adding hormone therapy to radiation therapy has been proven in randomized clinical trials to improve overall survival for men with intermediate- and high-risk prostate cancer. However, adding hormone therapy may reduce overall survival in men with pre-existing heart conditions, even if they have high-risk prostate cancer according to a new study just published online in advance of print in the International Journal of Radiation Oncology•Biology•Physics, the official scientific journal of ASTRO.

From 1991 to 2006, 14,594 men with prostate cancer were treated with brachytherapy-based radiation therapy. Of these, 1,378 (9.4 percent) had a history of congestive heart failure or myocardial infarction. Among these men with heart conditions, 22.6 percent received supplemental external beam radiation therapy and 42.9 percent received four months of androgen deprivation therapy to reduce testosterone in their bodies, which can help the cancer grow.

For the entire group of men with a history of heart problems, adding hormone therapy led to a significant increase in overall mortality. For men with pre-existing heart conditions and high-risk prostate cancer, researchers found that by 5 years, 31.8 percent of the men who received hormones had died compared to 19.5 percent of the men who did not receive hormone therapy.

“We found that for men with localized prostate cancer and a history of heart problems, treatment with hormones plus radiation was associated with a higher all-cause mortality than treatment with radiation alone, even for patients with high-risk malignant disease,” Paul L. Nguyen, M.D., lead author of the study and a radiation oncologist at the Dana-Farber/Brigham and Women’s Cancer Center in Boston, said. “Despite Phase III data supporting hormone therapy use for men with high-risk disease, the subgroup of men with a history of heart disease may be harmed by hormone therapy.”

He added, “Future research is necessary to understand the mechanisms of this effect. In the meantime, I encourage men with prostate cancer and a history of heart disease to talk to their doctor about the benefits and risks of hormone therapy.”

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